Nanomaterials and their hybrids with biological molecules are recognized to have potential applications in electronic, optics, genomics, proteomics, and biomedical and bioanalytical areas. The usefulness of these hybrid materials largely depends on how well can one achieve rational design based on specific binding between inorganic nanomaterials and biological molecules. It is generally recognized that the surfaces of many nanoparticles, such as Au, Ag, Pt and Cu are charged, which cause non-specific binding with biological molecules via electrostatic interactions. Alkyl thiol protected nanoparticles reduce the electrostatic interactions but induce hydrophobic interactions, another type of non-specific interaction. In addition, alkyl thiol protected nanoparticles are not soluble in water, which makes them non-compatible with biomolecules that require aqueous environment for activity. Prime et al. (Science (1991), 252(5009), 1164-7) and Lahiri et al. (Analytical Chemistry, 1999 Feb. 15, 71(4) 777-90) both describe a method to prepare a model system for the adsorption of proteins on surfaces by preparing self-assembled monolayers of alkanethiols on gold films. Singh et al. describes a method for using gold nanorods to extract groups of biomolecules, using derivatized alkanethiols (U.S. Patent Appl. 20020034827).
Nanoparticles coated with tiopronin (N-2-mercaptopropionyl-glycine, TP) have the advantage of being water-soluble, but are subject to non-specific binding of biomolecules. Templeton et al. (JACS, 1999, 121, pg 7081) prepared gold clusters coated with single monolayers of tiopronin and acidic, water soluble ligands. Gold and silicon surfaces have been coated with ethylene glycol derivatives and have been shown to resist protein binding on a flat gold surface. Additionally gold nanoparticles coated with polyethylene glycol have been shown to be water soluble. However, the neutral glycols cannot react easily with biomolecules, and the monolayer thickness is not well defined, particularly with large polymer chains.
Foos et. al (Chem. Mater. (2002), 14, pg 2401-2408) have prepared a gold nanocluster coated with short chain ethylene glycol oligomers in a monolayer. However, the authors used a two-phase organic solvent system (as opposed to an aqueous/organic mixed solvent) for preparation and not all of the coated particles were found to be water-soluble.
Applicants have solved the deficiencies in the prior art by constructing a water soluble, metallic nanoparticle with a mixed monolayer, comprising a capture component and a shielding component with well defined thickness or length using a single phase organic/aqueous solvent system. The shielding component, (thiolated ethylene glycol short chain oligomers with well defined thickness or length), functions to minimize the non-specific interaction between nanoparticles and biological molecules, whereas the capture coating component, (e.g. tiopronin), serves as ligand to engage biological molecules specifically.